Increased survival time after delayed histamine and prostaglandin blockade in a porcine model of severe sepsis-induced lung injury.
A combination of cimetidine, diphenhydramine, and ibuprofen has been shown to be an effective treatment in a porcine model of septic acute lung injury. The present study was designed to evaluate this therapy in a delayed treatment survival model. Three groups of animals were studied: a control group (C, n = 6) received a sham infusion of 0.9% saline; a septic group (Ps, n = 5) received a continuous infusion of live Pseudomonas aeruginosa organisms; and a treatment group (CID, n = 6) received P. aeruginosa plus cimetidine 150 mg, ibuprofen 12.5 mg/kg, and diphenhydramine 10 mg/kg given at 90 min after P. aeruginosa infusion, and hourly thereafter. Group Ps developed fulminant acute lung injury and hypodynamic septic shock. CID therapy ameliorated temporarily the progressive course of hypoxemia and increased extravascular lung water (EVLW), delayed the onset of cardiovascular deterioration, and improved significantly survival time. It was concluded that CID therapy given at 90 min after the onset of lethal continuous P. aeruginosa infusion improved significantly animal survival time by improving temporarily hypoxemia and increase in EVLW and delaying cardiovascular collapse.
Byrne
K
K
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0519.
Sielaff
T D
TD
Michna
B
B
Carey
P D
PD
Blocher
C R
CR
Vasquez
A
A
Sugerman
H J
HJ
D000818:Animals; D002927:Cimetidine / Q000008:administration & dosage; D004155:Diphenhydramine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D015633:Extravascular Lung Water / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006633:Histamine Antagonists / Q000627:therapeutic use*; D007052:Ibuprofen / Q000008:administration & dosage; D011448:Prostaglandin Antagonists / Q000627:therapeutic use*; D011552:Pseudomonas Infections; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D012772:Shock, Septic / Q000150:complications*; D013552:Swine
D006633:Histamine Antagonists; D011448:Prostaglandin Antagonists; D002927:Cimetidine; D004155:Diphenhydramine; D007052:Ibuprofen